Omega-3 Health Research in Focus

The global market for packaged EPA/DHA omega-3 products is expected to reach $34.7 billion by 2016, driven in large part by consumer demand for omega-3 supplements and omega-3-enhanced functional foods, says the market research firm Packaged Facts. Fish is the most common source of DHA and EPA omega-3 fatty acids but other plant sources like algae, chia, and flax have also found acceptance, thanks to their EPA and short-chain ALA content. Dovetailing with the uptick in demand is growing volume of scientific research aimed at identifying and substantiating omega-3’s many health benefits, which include cardiovascular, cognitive, and mood support, to name a few.

“Medical experts continue to be quite positive regarding human consumption and the nutritional value of the omega-3s,” says Stacy Peterson, president of Connoils LLC (Big Bend, WI), a supplier of plant-based DHA ingredients. “Since the body cannot make omega-3 essential fats, they must come from another source: one’s diet or supplements.”

Favorable Studies

The health claim most synonymous with omega-3 supplementation is cardiovascular support, and research in this area has been predominantly positive.

Harry Rice, PhD, vice president of regulatory and scientific affairs at the Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City, UT), points to a recent Annals of Internal Medicine cohort study as one of the most current and important to link blood levels of omega-3 fatty acids to a reduction of cardiovascular risk factors. “Omega-3 levels were associated with a lower total mortality (27% lower risk when comparing lowest intakes to highest intakes) which translated into living an extra two-plus years,” says Rice. “The findings support an average target dietary range of 250–400 mg of EPA and DHA per day.”

Cognitive health is the second most researched health benefit associated with omega-3 consumption, and there is heightened interest in how DHA and EPA impact children. The most recent and well-publicized studies in this population group stem from the DHA Oxford Learning and Behavior study (DOLAB).

The initial DOLAB trial suggested that DHA supplementation was “a safe and effective way to improve reading and behavior” in underperforming children.  More recently, an observational study using the same group of children observed that low blood DHA levels were linked to decreased reading ability and memory performance in children. The analysis was funded by a grant from fish oil supplier DSM Nutritional Products (Parsippany, NJ).

“The outcomes for this study were so exciting that enrollment has already begun for a follow-up study to further investigate this exciting area,” exclaims DSM marketing manager Megan Gorczyca.

In a similar vein, a University of Kansas study, published in April, assessed the effect of long term DHA supplementation on the cognitive development of infants and found DHA might lengthen gestation and increase birth size. “The results of the study add to previous evidence that omega-3 fatty acid supplements help to extend pregnancy, providing more time for babies to develop with a better long-term health outlook,” Gorczyca says. “The Kansas study looked at 350 women, who either took an algal-DHA supplement or a placebo three times a day while pregnant. Upon the conclusion of the study, researchers found that participants taking the DHA supplements tended to have slightly larger, heavier babies and tended to give birth about three days later than the placebo group.”

But EPA and DHA aren’t the only beneficial components of omega-3 fatty acids. Research into the health benefits of short-chain ALA is also proving fruitful.

“There are a relatively high number of in vitro and animal studies…which have been generally underappreciated, showing that ALA exerts identical effects as does DHA in a number of different physiological paradigms, although in most cases, longer treatments or higher concentrations of ALA are needed as compared to when dietary DHA is consumed,” says Carolina Chica, nutrition research and regulatory issues manager for Benexia, a chia-derived omega-3 ingredient supplied by Proprietary Nutritionals Inc. (Kearny, NJ). “These results suggest that ALA may, in many cases, use an identical mechanism as DHA to exert its action, while in other cases its effect is through its conversion to DHA.”

Unfavorable Studies

Despite an overwhelmingly positive collection of studies, there have been noteworthy research outcomes-and subsequent publicity-questioning high omega-3 intake. A Journal of the National Cancer Institute study made controversial waves in July with its assertion that phospholipid fatty acids may increase the prevalence of prostate cancer.

The study, which was roundly rebuked by the dietary supplement industry, utilized the same group of men over the age of 55 who took part in SELECT (the Selenium and Vitamin E Cancer Prevention Trial) from 2001 to 2004. The consensus of the backlash was that the study wasn’t specifically designed to assess the relationship between omega-3 fatty acid intake and prostate cancer.

“If the findings from this study were true, then the prevalence of prostate cancer would correlate positively with seafood consumption-and it doesn’t,” says Rice. “For example, in Japan and Scandinavia, seafood consumption is high, but the prevalence of prostate cancer is not.”

An equally unfavorable reception followed the release of the Age-Related Eye Disease Study 2 study (AREDS2), which examined the efficacy of lutein, zeaxanthin, and omega-3 fatty acids on age-related macular degeneration (AMD). “This study did not assess primary prevention, which is always more effective than treatment,” says Rice.

Finally, earlier this year, a New England Journal of Medicine double-blind, placebo-controlled clinical trial concluded that omega-3 therapy offered no benefit for patients who had cardiovascular risk factors. The more than 12,000 men and women enrolled in the trial, all of whom had multiple cardiovascular risk factors, were randomly dosed with either 1 g of omega-3 daily or an olive oil placebo. They were followed for five years.

“Compared to past studies demonstrating cardiovascular benefits of omega-3s, subjects in recent trials, including this one, received better pharmaceutical treatment…[and] such treatment makes it much less likely to be able to see a benefit with omega-3s,” says Rice. “To put this into perspective, the addition of another drug would unlikely yield an additional benefit without drastically increasing the power. The omega-3s are not failing to have effect(s); rather, the studies are underpowered and there is a failure to detect effect(s).”

Rice adds that, sometimes, even studies that were highly publicized for reaching neutral conclusions can have a silver lining. Case in point: a recent meta-analysis conducted to assess the role of omega-3 supplementation on major cardiovascular outcomes. “The authors failed to report that fish oil supplementation significantly reduced the risk for cardiac death by 9%,” says Rice. “Instead, they reported that there was no effect of fish oil on cardiovascular disease. This happened because they inappropriately corrected for multiple testing, a practice which is seldom done in meta-analyses.”

Establishing Krill Connections

While research on fish-source omega-3s is abundant, research on other-source omega-3 continues to emerge. The focus for Aker BioMarine (Issaquah, WA) has been krill-source omega-3.

One study  set out to determine if a lower dose of krill oil could render the same triglyceride-lowering effect as a standard dose of fish oil. Aker’s Superba brand krill oil, and fish oil and a placebo were randomly dosed to 113 subjects with normal or slightly increased total blood cholesterol and/or triglyceride levels for seven weeks. Daily supplementation of total EPA and DHA was approximately 37% less in the krill oil group than in the fish oil group. The krill oil group reflected a 45% higher total EPA and DHA plasma level than in the fish oil group. The subjects also showed decreased plasma triglyceride levels.

Another randomized, double-blind, placebo-controlled, multi-center, triglyceride-oriented study that has not yet been published, but it examined krill’s ability to lower triglycerides without raising LDL (the outcome in some fish oil trials). The trial involved 300 subjects with high triglyceride levels. Aker says the results were positive: a beneficial lowering of triglycerides without raising LDL.

The Search for New Sources

Cargill (Minneapolis) and BASF (Philadelphia) have joined forces to develop new cost-effective canola varieties that will accumulate EPA and DHA omega-3 fatty acids in the seed oil. Lorin DeBonte, Cargill’s assistant vice president R&D for oils and shortenings, says the goal of the partnership to offer a cost-effective, new dietary source of EPA and DHA that can enable food, pharmaceutical, and nutritional supplement manufacturers to create a broad array of products that deliver the potential heart and cognitive health benefits of omega-3 fatty acids.